Tissue regeneration involves known markers such as metalloproteinases and growth factors, including without limitation HGF (hepatocyte growth factor), LOX (lysyl oxidase), MMP1, MMP2, MMP9, MMP13, PLAT (tPA), PLAU (uPA), Serpin A1 (AAT), Serpin E1 (PAI-1), TIMP3, ILK (integrin-linked kinase).
The impact of HGF in tissue repair and regeneration is well described in the scientific review: The discovery of Hepatocyte Growth factor (HGF) and its significance for cell biology, life sciences and clinical medicine from Nakamura and Mizuno, Proc. Jpn. Acad. Ser B86 (2010). This review article describes the role of HGF in tissue regeneration in liver, kidney, heart, and lung. Also, HGF is required for self-repair after injuries of skin, stomach, intestine, muscle and cartilage and is also involved in organ development (organogenesis including mitogenesis, motogenesis and morphogenesis). HGF is also implicated in the regeneration of injured tissue by its modulation of regeneration enzyme (metalloproteinases) and also by inhibiting apoptosis. Furthermore, recent reports suggest that HGF has an anti-inflammatory action and attenuated cellular senescence. Thus, HGF gene therapy or compound increasing HGF expression and secretion might be an anti-aging therapy in cardiovascular diseases (Nakagami, Morishita, 2009). HGF is also known to accelerate would healing (Li et al., BioMed Research International, Volume 2013 (2013), Article ID 470418.
Regeneration enzymes (including metalloproteinases) are also very important in repair and regeneration of injured organs.
A recent publication (abstract presented at Plastic surgery meeting 2014 by Radtke et al. entitled Single treatment With Alpha-1 antitrypsin Enhances Nerve Regeneration After Peripheral Nerve Injury) has demonstrated that AAT improves peripheral nerve regeneration. The application of AAT into an acute axotomy model led to the significantly improved axonal regeneration and re-myelination than compared control animals. Moreover, not only histological, but also functional improvement was observed following direct injection of AAT after acute peripheral nerve lesion. Their results indicate that AAT delivered into injured peripheral nerve participate in neural repair.
Cutaneous aging is a complex phenomenon responsible for progressive changes of the skin. Aging of the skin results from two processes: (1) an intrinsic process, corresponding to chronological aging, and (2) an extrinsic process resulting mainly from the deleterious effect of exposure environmental stresses. Genetic, UV exposure, climatic factors (harshness/wind/cold/warm), pollution (chemical, free radicals, contaminant, nitrogen oxide, metals), alcohol consumption or smoking are factors involved in cutaneous aging.
Exposure to irritants compromises the barrier function of the stratum corneum and decreases its ability to protect the skin against environmental stresses (e.g., ultraviolet irradiation, infections agents, etc.). Repeated and prolonged exposition to environmental irritants results in denatured skin proteins, disorganization of the lipid lamellae layers, removal of the protective intercellular lipids, loss of natural moisturizing factors and decreased cohesion between cells. These damages are also responsible for the loss of function of the enzymes responsible for desquamation of corneocytes. There is accentuation of these problems with exposure to pollution, cold, sun, wind, low humidity or chemical agents. An irritant is any agent that is capable of producing cell damage if there exposure for sufficient time and in sufficient concentrations. The severity of the damage is dependent of the type and intensity of exposure to these irritating factors. There are also endogenous factors that make one susceptible to damaged skin by external factors. These factors include having active skin disease such as eczema, inherited dry skin conditions, a previous history of skin disease, sensitive skin and/or older age.
Novel compounds and medicaments are needed to stimulate the tissue self-repair and the tissue regeneration in injured organ.